P1318: CLOSTRIDIUM BUTYRICUM MIYAIRI 588 CONTRIBUTES TO THE MAINTENANCE OF INTESTINAL MICROBIOTA DIVERSITY EARLY AFTER HEMATOPOIETIC CELL TRANSPLANTATION.
Authors: Kentaro Fukushima, Hayami Kudo, Kentaro Oka, Atsushi Hayashi, Makoto Onizuka, Shinsuke Kusakabe, Akihisa Hino, Motomichi Takahashi, Kiyoshi Takeda, Masaki Mori, Kiyoshi Ando, Naoki Hosen
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: The intestinal microbiota plays an essential role in maintaining homeostasis in the body, and the relationship between intestinal microbiota and diseases has been clarified not only in malignant diseases but also in lifestyle-related diseases and neuropsychiatric disorders. In haematopoietic stem cell transplantation (HSCT), a curative therapy for haematologic malignancies, the intestinal microbiota has been shown to play a role in the prognosis, transplant outcome, and complications such as graft-versus-host disease (GVHD). Aims: To evaluate the direct and indirect effects of Clostridium butyricum MIYAIRI 588 (CBM588) as a probiotic on intestinal microbiota in the early post-HSCT period. Methods: This prospective observational study was approved by the institutional review board of Osaka University Hospital and Tokai University Hospital and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients prior to specimen collection. A total of 38 adult patients who underwent allogeneic HSCT between May 2006 and May 2017 were included. Baseline faecal samples were collected on day 8 before HSCT and prior to the start of HSCT conditioning regimens. Thereafter, 196 samples were taken sequentially every week from the start of the conditioning regimen to 35 days after HSCT. For all samples, 16S rRNA deep sequencing was performed using MiSeq (Illumina), followed by analysis of the QIIME2 platform version 2019 and comparison with the SILVA database. Quantification abundance of C. butyricum was also confirmed by qPCR. Results: Alpha diversity of the faecal microbiome in the CBM588 administration group (CBM588) and Ctrl groups (Ctrl) during the early post-transplant period. indicated a significant difference between the Shannon index of the microbiome of patients in the CBM588 and Ctrl groups on days 7, 14, 21, and 35 (p<0.01) post-HSCT using the Mann–Whitney U test. Principal Coordinate Analysis based on unweighted UniFrac distance of the microbiome across time points revealed significant differences at day 7(p=0.015), 14(p=0.013), 21(p=0.007), post-HSCT. The copy number of C. butyricum was significantly higher in the CBM588 group than in the control group. These results indicate that C. butyricum effectively reached the colon in the CBM588 group. Moreover, the genus Bacteroides dominant group, cluster III microbiota, was reported to be a risk factor for acute GVHD, and CBM588 reduced the cluster III microbiota in this study. Furthermore, the CBM588 group had a 1-year survival rate of 84.6%, while the control group had a survival rate of 71.4%; however, the difference was not significant, partly due to the sample size of this study. Summary/Conclusion: CBM588 contributes to the maintenance of intestinal microbiota diversity early after haematopoietic cell transplantation. Furthermore, CBM588 effectively reduced the cluster III microbiota at risk for acute GVHD and showed the potential for improved the prognosis. We are planning prospective investigations are required to test it. Keywords: Allogeneic hematopoietic stem cell transplant, Supportive care